Phage-related symbiosis and antagonism shape gut ecosystem dynamics in Lachnospiraceae and Bacteroidaceae

The human gut microbiota is shaped by intricate, yet poorly resolved interactions among bacteria, as well as their relationship to bacteriophages. However, resolving this complex interaction and dynamics has been limited by the challenges in genome recovery and functional characterization. We develop culture-enriched metagenomic co-barcoding sequencing (cMECOS), obtain 5,006 high- or medium-quality (HMQ) metagenome-assembled genomes (MAGs) and reconstruct bacteria-phage interaction networks via CRISPR spacer mapping. This framework uncovers two ecologically distinct, inter-specific bacterial networks: a Lachnospiraceae-dominated community associates with temperate phages and is characterized by metabolic cross-feeding and a Bacteroidaceae-dominated community linked to virulent phages and marked by resource competition. Both network architectures are disrupted in both inflammatory bowel disease (IBD) and obesity (OB), underscoring their role in ecosystem stability. Our work establishes cMECOS as a powerful platform for deciphering complex microbiome interactions and identifies phage-related bacterial networks as critical regulators of gut homeostasis, providing a foundation for phage-informed therapeutic development.